A novel protein has been identified on the surface of mycobacteria including M. tuberculosis, the causative agent of TB, which appears to promote the interaction of mycobacteria with host cells. Methods have been developed for the purification of this unique protein. The gene has been cloned and sequenced from both M. tuberculosis and M. bovis and no significant homology has been found with any other gene. Evidence suggests that this protein is glycosylated and that this effects both function and immunogenicity. Important binding sites and immunological epitopes have been identified and characterized. Specific regions that interculate into the bacterial membrane, that form coiled-coil initiated interactions, and that bind to proteoglycans have been identified. The role of this protein in attachment of mycobacteria to host tissues and in other bacterial interactions continues to be investigated in detail. The gene has been investigated as a DNA vaccine candidate. We are developing an intranasal challenge model in mice to investigate the role of HBHA in protective immunity. Initial results suggest that monoclonal angibodies against HBHA decrease the colonization of the trachea and lungs by pathogenic mycobacteria as well as dissemination of bacteria to the spleen. The role of HBHA in passive and active immunization against animal models of TB will be further investigated.